EFFECT OF LEVOTHYROXINE ON THE STATE OF OXIDANT-ANTIOXIDANT BALANCE IN PATIENTS WITH COMBINED COURSE OF HYPERTENSION, TYPE 2 DIABETES AND SUBCLINICAL HYPOTHYROIDISM

Nemtsovа V. D.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Aim: to evaluate the effect of levothyroxine replacement therapy on oxidative stress in patients with combined course of arterial hypertension (AH), type 2 diabetes mellitus (DM2T), and subclinical hypothyroidism (SHT). Object and methods. The study included 40 patients (9 males and 31 females) aged 44 to 75 years (mean age 59.3 ± 3.5 years) with stage II hypertension in combination with DM2T and SHT. The presence of SHT that developed as a result of autoimmune thyroiditis (AIT) and TSH levels in the range 6.0-10.0 µMU/ml in screening was an obigatory criterion. The control group consisted of 30 gender and age-representative patients who did not have cardiovascular disease and endocrinopathies. Thyroid metabolism, glutathione peroxidase (GPO) activity, levels of sulfhydryl groups (SH-groups), malonic dialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) in serum were determined. Ultrasound examination of the thyroid gland was performed on the “LOGIQ 5” according to the standard method. After determining the TSH level, patients were prescribed levothyroxine at doses of 12.5 to 50 μg/day with gradual dose titration (21 day titration step) until euthyroidism was achieved. Observation period was1 year. Statistical processing of data was performed using the computer program SPSS 21.0. Results. The presence of significantly higher levels of MDA and significantly elevated (almost 2.3-fold) levels of 8-OHdG in the patients of the study group indicates a pronounced stimulation of oxidative processes in such a polymorbid clinical situation. Stimulation of the oxidation processes occurs against the background of inhibition of the antioxidant system, which is manifested by a significantly decrease in levels of both GPO (p <0.05) and SH-groups (p <0.05). Correlation analysis revealed a positive association between TSH and GPO levels (r = 0.226, p = 0.029) and a negative relationship between TSH and SH group levels (r = -0.227, p = 0.028). Conducting a one-way ANOVA revealed the presence of an effect of TSH levels on the level of GPO (p = 0.039) in this category of patients. The administration of levothyroxine was accompanied by a decrease in MDA and 8-OHdG levels at the end of the observation period, although these changes were unreliable, and a significant increase in the antioxidant protection indexes – GPO (p = 0.016) and SH-groups (p = 0.001). Conclusions. The presence of a combined course of arterial hypertension, type 2 diabetes and subclinical hypothyroidism with TSH in the range 6.0-10.0 µMUd/ml is accompanied by the presence of pronounced oxidative stress. Prescribing levothyroxine replacement therapy to patients with such polymoride pathology leads to an improvement in the oxidant-antioxidant balance by intensifying the antioxidant defense mechanisms to a greater extent than by inhibiting the oxidative processes.

hypertension, type 2 diabetes, subclinical hypothyroidism, levothyroxine, oxidative stress.

1. Kalinchenko SJu, Gusakova DA, Vorslov LO, Tishova JuA, Tjuzikov IA, Nizhnik AN. Okislitel’nyj stress i starenie. Rol’ vitamina D v geneze associirovannyh s vozrastom zabolevanij. Jeffektivnaja farmakoterapija. 2016;2:8-14. [in Russiаn].
2. Lodovici M, Bigagli E, Luceri C, Mannucci E, Rotella CM, Raimondi L. Gender-related drug effect on several markers of oxidation stress in diabetes patients with and without complications. Eur J Pharmacol. 2015;5(766):86-90. DOI: 10.1016/j.ejphar.2015.09.041
3.  Di Minno A, Turnu L, Porro B, Squellerio I, Cavalca V, Tremoli E, et al. 8-Hydroxy-2-Deoxyguanosine Levels and Cardiovascular Disease: A Systematic Review and Meta-Analysis of the Literature. Antioxid Redox Signal. 2016 Apr 1;24(10):548-55. DOI: 10.1089/ars.2015.6508
4. Kim JY, Kim OY, Paik JK, Kwon DY, Kim H-J, Lee JH. Association of age-related changes in circulating intermediary lipid metabolites, inflammatory and oxidative stress markers, and arterial stiffness in middle-aged men. Age (Dordr). 2013;35(4):1507-19. DOI: 10.1007/s11357-012-9454-2
5. Cheserek MJ, Wu GR, Ntazinda A, Shi YH, Shen LY, Le GW. Association Between Thyroid Hormones, Lipids and Oxidative Stress Markers in Subclinical Hypothyroidism. J Med Biochem. 2015 Jul;34(3):323-31. DOI: 10.2478/jomb-2014-0044
6. Nasmi Niknam, Noushin Khalili, Elham Khosravi, Mohsen Nourbakhsh. Endothelial dysfunction in patients with subclinical hypothyroidism and the effects of treatment with levothyroxine. Adv Biomed Res. 2016;5:38.
7. Elisabeth Mahase. Subclinical hypothyroidism: doctors shouldn’t routinely prescribe hormones. BMJ. 2019;365:l2262. DOI: https://doi. org/10.1136/bmj.l2262
8. Nemtsova V, Bilovol O, Shalimova A. Vascular endothelial growth factor as a marker of endothelial dysfunction in poly- and comorbidity: focus on hypertension, type 2 diabetes mellitus and subclinical hypothyroidism. Arterial Hypertension. 2019;23(2):98-104.
9. Nekrasova A, Shcherbatyuk TG, Davydenko DV, Ledentsova OV, Strongin LG. Osobennosti perekisnogo okisleniya lipidov i belkov pri autoimmunnom tireoidite bez i s minimalnoy tireoidnoy disfunktsiyey. Klinicheskaya i eksperimentalnaya tireoidologiya. 2011;4(7):38-43. [in Russiаn].
10. Chen Y, Wu G, Xu M. The effect of L-thyroxine substitution on oxidative stress in early-stage diabetic nephropathy patients with subclinical hypothyroidism: a randomized double-blind and placebo-controlled study. Int Urol Nephrol. 2018 Jan;50(1):97-103. DOI: 10.1007/s11255- 017-1756-y
11. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J. of Hypertension. 2013;31(7):1281-357.
12.  Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015 Jan;38(1):140-9.
13. Pearce SH, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. European Thyroid Journal. 2013;2:215-28.
14. Erem C, Suleyman AK, Civan N, Mentese A, Nuhoglu İ, Uzun A, et al. The effect of L-thyroxine replacement therapy on ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hypothyroidism. Endocr Res. 2016 Nov;41(4):350-60. DOI: 10.3109/07435800.2016.1163722
15. Mutlu S, Parlak A, Aydogan U, Aydogdu A, Soykut B, Akay C, et al. The effect of levothyroxine replacement therapy on lipid profile and oxidative stress parameters in patients with subclinical hypothyroid. Arch Pharm Res. 2013 Aug 8. [Epub ahead of print] DOI: 10.1007/s12272-013- 0227-y
16. Redford С, Vaidya В. Subclinical hypothyroidism: Should we treat? Post Reprod Health. 2017;23(2):55-62. DOI: 10.1177/2053369117705058
17. Biondi В, Cappola A, Cooper D. Subclinical Hypothyroidism: A Review. JAMA. 2019;322(2):153-60. DOI: 10.1001/jama.2019.9052
18. Razvi S, Weaver JU, Butler TJ, Pears ShS. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events and mortality. Arsh Intern Med. 2012;172(10):811-8. DOI: 10.1001/archinternmed.2012.1159

«Bulletin of problems biology and medicine» Issue 4 Part 1 (153), 2019 year, 126-130 pages, index UDK 616.12-008.331.1+616.379-008.64+616.441-008.64]-085

10.29254/2077-4214-2019-4-1-153-126-130